Treating seizures: bumetanide doesn’t seem to work

One of the many frustrating things in neonatology is the treatment of convulsions.

As Gerry Boylan and Ronit Pressler wrote in the introductory section of the excellent issue of Seminars in Fetal and Neonatal Medicine which was all about neonatal seizures,

“Neonatal seizures continue to pose a challenge for clinicians worldwide because they are difficult to diagnose and treat and are associated with poor outcomes.” We have been using this statement, or something very similar, to introduce the topic of neonatal seizures when we give lectures or write papers for the last fifteen years and in that period of time, unfortunately, very little has changed in the management and outcome of neonatal seizures.

It is hard to know if the treatments we give are much use. Does phenobarbitol actually work? A truly evidence-based answer to that question would be “who the hell knows?” It might be a bit less useless than some other drugs, but I don’t think there is good evidence that it works at all. Clinical seizures stop in around 50% of babies after phenobarb, but maybe they would have stopped anyway. EEG documented, electrical seizures often don’t stop after phenobarb, and babies can even have non-convulsive status epilepticus after phenobarb.

Bumetanide is a loop diuretic that is an effective anticonvulsant in neonatal rats. Unfortunately it doesn’t seem to work in human neonates. Pressler RM, et al. Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO): an open-label, dose finding, and feasibility phase 1/2 trial. The Lancet Neurology. 2015;14(5):469-77. Although they only entered a small number of infants (14) into the study, they were unable to show efficacy, and they had a higher than expected rate of hearing loss.

I think this is great.

Not the result, of course, it would have been really great to find an effective, safe anticonvulsant. But I think it is great that this study was done, that the group was put together and the infrastructure created to get this very high quality investigation performed. Lets hope that the group will stay active, and will be able to evaluate other agents that are creeping into use without good studies. Like levetiracetam, that I can never spell correctly, (so I hope that the site I just copied that from was correct) or topiramate, that I would vote for as I can remember how to spell it.


About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
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